Reaktion #60278

Reaktionsgleichung

HOBT

triethylamine

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid

O-(2-vinyloxy-ethyl)-hydroxylamine

EDCI

→

pure desired product

Ausbeute 79.0%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide

Ausbeute 79.0%

Lösungsmittel

N,N-dimethylformamide

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige(2-3 days)
2. 2
   workup.ADDITIONThe reaction mixture is poured into a separatory funnel
3. 3
   Sonstigethe layers separated
4. 4
   WaschenThe ethyl acetate layer is washed successively with aqueous saturated NH4Cl (2×), brine (1×), aqueous saturated sodium bicarbonate (2×), water (1×), and brine (1×)
5. 5
   Trocknendried (Na2SO4)
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe resulting solid is purified by FCC (eluting with 15:1 methylene chloride:methanol)

Vorschrift

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid 11r (0.11 g, 0.23 mmol) is dissolved in N,N-dimethylformamide (2 mL). HOBT (0.037 g, 0.27 mmol) and triethylamine (0.094 mL, 0.68 mmol) are added. Then O-(2-vinyloxy-ethyl)-hydroxylamine (0.028 g, 0.27 mmol) and EDCI (0.056 g, 0.29 mmol) are added and the reaction mixture is stirred at room temperature under N2 until HPLC shows the reaction is complete (2-3 days). The reaction mixture is poured into a separatory funnel, diluted with ethyl acetate and water and the layers separated. The ethyl acetate layer is washed successively with aqueous saturated NH4Cl (2×), brine (1×), aqueous saturated sodium bicarbonate (2×), water (1×), and brine (1×), dried (Na2SO4) and concentrated under reduced pressure. The resulting solid is purified by FCC (eluting with 15:1 methylene chloride:methanol) to yield 0.039 g (79%) of the pure desired product as an off-white solid. MS ESI (+) m/z 567, 569 (M+, Br pattern) detected.

Quelle